A variety of agents have been administered to the cerebrospinal fluid (CSF), such as through intracerebroventricular (ICV) or intrathecal (IT) bolus infusion. Typically, these agents are administered acutely through a single, bolus infusion at flow rates in the range of about 0.5 to 12 ml/min. At such high delivery rates, the agents can achieve wider distribution within the central nervous system (CNS), albeit transiently.
However, at lower flow rates, such as less than 1 ml/day, studies report that the distribution of the agent in the CSF is limited. For example, one study reported the distribution of a small molecule agent within the CSF following IT infusion at a rate of 20 microliters per hour was limited to less than 5 cm of the spinal cord relative to the infusion site.
In many situations and for many reasons, it would be desirable to administer an agent at a low flow rate to a subject's CSF; e.g. when using a chronically implanted infusion device, but achieve broad distribution of the agent in the subject's CNS.